Lanthipeptides are post-translationally modified peptide with a variety of biological activities. Nisin, its best known member, has been used for decades in the food industry without significant development of resistance. Other lanthipeptides are under investigation or in clinical trials for the treatment of cystic fibrosis and for the treament of multi-drug resistant bacteria. In this grant application we seek to extend our past success towards the use of the biosynthetic machinery as tools for biotechnology and to better understand their mechanism of substrate recognition and catalysis. Our goals are: 1. Understand the enzymes involved in lanthipeptide biosynthesis. 2. Engineer efficient processes to use posttranslationally modified peptide natural products for various applications. 3. Investigate new posttranslationally modified peptide natural products.